R. Tajima et al. / European Journal of Medicinal Chemistry 46 (2011) 1374e1381
1379
layers were dried over Na2SO4. Filtration and concentration fol-
lowed by silica gel chromatography (45% EtOAc in hexane) gave the
title compound 20 (117 mg, 71% from 19) as a white solid. IR (film)
CDCl3) d 170.0 (C),169.88 (C),169.86 (C),169.8 (C),169.4 (C),169.3 (C),
158.2 (C),157.3 (C),155.5 (C),154.8 (C),137.2 (C),137.0 (C),130.6 (CH),
130.2 (CH), 128.53 (CH), 128.48 (CH), 127.9 (CH), 127.8 (CH), 127.5
(CH), 127.3 (CH), 126.5 (C), 123.1 (C), 110.4 (CH), 105.2 (CH), 104.6
(CH), 100.3 (CH), 98.5 (CH), 97.9 (CH), 70.7 (CH), 70.2 (CH2), 70.1
(CH2), 69.8 (CH), 69.7 (CH), 69.1 (CH), 68.5 (CH2), 68.2 (CH2), 61.8
(CH2), 61.4 (CH2), 30.1 (CH2), 29.9 (CH2), 20.8 (CH3). ESIHRMS m/z
965.3307 [M þ Na]þ (calcd for C50H54NaO18, 965.3208).
nmax 3032, 1753, 1506, 1223, 1039, 737 mꢃ1 1H NMR (400 MHz,
.
CDCl3)
d
7.40 (10H, m, ArH), 7.04 (1H, d, J ¼ 8.3 Hz, ArH), 6.96 (1H, d,
J ¼ 8.8 Hz, ArH), 6.62 (1H, d, J ¼ 2.4 Hz, ArH), 6.51 (1H, dd, J ¼ 2.4,
7.3 Hz, ArH), 6.48 (2H, m, ArH), 5.52 (1H, bs, OH), 5.22 (1H, t,
J ¼ 7.8 Hz, CH), 5.15 (1H, dd, J ¼ 6.4, 7.8 Hz, CH), 5.13 (2H, s, CH2),
5.09 (1H, d, J ¼ 6.4 Hz, CH), 5.01 (2H, s, CH2), 4.99 (1H, m, CH), 4.20
(1H, dd, J ¼ 4.9, 12.2 Hz, CH2), 3.49 (1H, dd, J ¼ 7.8, 12.2 Hz, CH2),
2.76 (4H, s, CH2), 2.08 (9H, m, CH3). 13C NMR (100 MHz, CDCl3)
4.1.13. 20,40-Dihydroxy-2,4-di(
Bibenzyl 21 (19 mg, 20 mol) in EtOAc (2 mL) was hydrogenated
b-D-xylopyranosyl)bibenzyl (3)
m
d
170.1 (C), 169.9 (C), 169.5 (C), 158.5 (C), 157.0 (C), 156.1 (C), 154.9
over 20% Pd(OH)2 on carbon (3 mg) for 12 h. Filtration through
Celite 535 and concentration in vacuo followed by silica gel chro-
matography (70e80% EtOAc in hexane) gave the phenol as a white
solid, which was used in the next step without further purification.
To cold (0 ꢀC) and stirred solution of the phenol in MeOH (4 mL)
(C), 136.9 (C), 136.5 (C), 130.5 (C), 130.2 (C), 128.7 (CH), 128.6 (CH),
128.1 (CH), 128.0 (CH), 127.5 (CH), 127.4 (CH), 122.8 (C), 122.4 (C),
108.6 (CH), 105.6 (CH), 104.6 (CH), 100.8 (CH), 98.6 (CH), 70.8 (CH),
70.1 (CH2), 68.5 (CH), 61.8 (CH2), 31.2 (CH2), 30.8 (CH2), 20.7 (CH3).
ESIHRMS m/z 683.2473 [M ꢃ H]ꢃ (calcd for C39H39O11, 683.2492).
was added 100 mL of NaOMe (5.2 M in MeOH) slowly. After being
stirred for 0.5 h at 0 ꢀC, the resultant solution was neutralized with
Amberlite IR-120 (Hþ). Filtration and concentration followed by
solid phase extraction with Sep-Pak Plus C-18 cartridge (0e40%
MeCN in H2O) gave the crude bibenzyl that was further purified by
4.1.11. 2,20,40-Trihydroxy-4-
b-D-xylopyranosylbibenzyl (2)
Bibenzyl20(96mg, 0.12mmol)inEtOAc(2mL)washydrogenated
over20% Pd(OH)2 oncarbon(24 mg)for12h. FiltrationthroughCelite
535 and concentration in vacuo followed by silica gel chromatog-
raphy (60e70% EtOAc in hexane) gave the phenol as a white solid,
which was used in the next step without further purification.
To cold (0 ꢀC) and stirred solution of the phenol in MeOH (5 mL)
preparative RP-HPLC (15% MeCN in H2O, tR ¼ 12.5 min). The title
20
compound 3 (8.7 mg, 85%) was obtained as a colorless solid. [a]
D
ꢃ48.0 (c 0.05, MeOH). IR (Nujol) nmax 3350, 1508 cmꢃ1
.
1H NMR
(pyridine-d5, 400 MHz)
d
7.49 (1H, bs, ArH), 7.31 (1H, d, J ¼ 8.3 Hz,
was added 110
mL of NaOMe (5.2 M in MeOH) slowly. After being
ArH), 7.28 (1H, d, J ¼ 8.3 Hz, ArH), 7.04 (1H, d, J ¼ 8.3 Hz, ArH), 7.02
(1H, bs, ArH), 6.72 (1H, d, J ¼ 8.3 Hz, ArH), 5.52 (1H, d, J ¼ 5.4 Hz,
CH), 5.38 (1H, d, J ¼ 7.3 Hz, CH), 4.28 (8H, m, CH and CH2), 3.85 (1H,
t, J ¼ 9.8 Hz, CH2), 3.67 (1H, dd, J ¼ 8.8, 11.2 Hz, CH2), 3.43 (2H, m,
stirred for 0.5 h at 0 ꢀC, the resultant solution was neutralized with
Amberlite IR-120 (Hþ). Filtration and concentration followed by
solid phase extraction with Sep-Pak Plus C-18 cartridge (0e40%
MeCN in H2O) gave the crude bibenzyl that was further purified by
CH2), 3.30 (2H, m, CH2). 13C NMR (pyridine-d5, 100 MHz)
d 157.6 (C),
preparative RP-HPLC (20% MeCN in H2O, tR ¼ 7.5 min). The title
157.2 (C), 156.8 (C), 156.7 (C), 130.8 (CH), 130.1 (CH), 126.0 (C), 119.9
(C), 109.6 (CH), 106.7 (CH), 105.3 (CH), 103.2 (CH), 103.1 (CH), 102.7
(CH), 77.8 (CH), 77.6 (CH), 74.2 (CH), 70.3 (CH), 70.2 (CH), 66.6 (CH2),
66.5 (CH2), 30.90 (CH2), 30.86 (CH2). HRESIMS m/z 509.1649
[M ꢃ H]ꢃ (calcd for C24H29O12, 509.1659).
20
compound 2 (40 mg, 85%) was obtained as a colorless solid. [a]
ꢃ5.6 (c 0.17, MeOH). IR (Nujol) nmax 3520, 3350, 1595, 1510 cmꢃ1. 1DH
NMR (pyridine-d5, 400 MHz)
d
7.35 (1H, d, J ¼ 8.3 Hz, ArH), 7.33 (1H,
d, J ¼ 8.3 Hz, ArH), 7.22 (1H, d, J ¼ 2.4 Hz, ArH), 7.08 (1H, d,
J ¼ 2.4 Hz, ArH), 6.90 (1H, dd, J ¼ 2.4, 8.3 Hz, ArH), 6.80 (1H, dd,
J ¼ 2.4, 8.3 Hz, ArH), 5.44 (1H, d, J ¼ 6.8 Hz, CH), 4.31 (1H, m, CH),
4.28 (1H, m, CH2), 4.26 (1H, m, CH), 4.23 (1H, m, CH), 3.66 (1H, dd,
J ¼ 9.3, 10.2 Hz, CH2), 3.44 (4H, m, CH2). 13C NMR (pyridine-d5,
4.1.14. 4-(200,300,400,600-Tetra-O-acetyl- -glucopyranosyl)-20,40-diben-
b-D
zyloxy-2-hydroxybibenzyl (25)
To a cold (0 ꢀC) and stirred solution of bibenzyl 19 (50 mg,
100 MHz)
d
157.7 (C), 157.3 (C), 157.1 (C), 157.0 (C), 130.6 (CH), 130.4
0.12 mmol) and 2,3,4,6-tetra-O-acetyl-
chloroacetimidate (22) (140 mg, 0.30 mmol) in CH2Cl2 (2 mL) was
added 10 L of TMSOTf solution (0.11 M in CH2Cl2). After being stirred
a-D-glucopyranosyl tri-
(CH), 123.5 (C), 120.1 (C), 107.2 (CH), 106.6 (CH), 104.4 (CH), 103.3
(CH), 102.8 (CH), 77.8 (CH), 74.2 (CH), 70.3 (CH), 66.6 (CH2), 30.8
(CH2), 30.6(CH2). HRESIMS m/z 377.1234 [M ꢃ H]ꢃ (calcd for
C19H21O8, 377.1236).
m
for 5 min at 0 ꢀC, the resultant solution was poured into EtOAc
(100 mL) and washed with saturated aqueous NaHCO3 solution
(20 mL ꢂ 3) and brine (20 mL ꢂ 3). The aqueous layers were extracted
with EtOAc (20 mL ꢂ 3), and the combined organic layers were dried
over Na2SO4. Filtration and concentration followed by silica gel
chromatography (50e55% EtOAc in hexane) gave the title compound
4.1.12. 2,4-Di(200,300,400-tri-O-acetyl- -xylopyranosyl)-20,40-dibenzy-
b-D
loxybibenzyl (21)
To a cold (0 ꢀC) and stirred solution of bibenzyl 19 (87 mg,
0.20 mmol) and imidate 14 (387 mg, 9.2 mmol) in CH2Cl2 (5 mL) was
25 (66 mg, 74% from 19) as a white solid. [
a
]
23 ꢃ4.48 (c 1.46, CHCl3). IR
D
added 36
mL of TMSOTf solution (0.11 M in CH2Cl2). After being
(film) nmax 3033,1750,1503,1220,1040, 736 mꢃ1. 1H NMR (400 MHz,
stirred for 5 min at 0 ꢀC, the resultant solutionwas poured intoEtOAc
(60 mL) and washed with saturated aqueous NaHCO3 solution
(15 mL ꢂ 3) and brine (15 mL ꢂ 3). The aqueous layers were extracted
with EtOAc (15 mL ꢂ 3), and the combined organic layers were dried
over Na2SO4. Filtration and concentration followed by silica gel
chromatography (40e50%EtOAcinhexane)gavethe title compound
CDCl3)
d
7.39 (10H, m, ArH), 7.02 (1H, d, J ¼ 7.8 Hz, ArH), 6.95 (1H, d,
J¼ 7.8Hz, ArH),6.62(1H, d,J¼ 2.4Hz,ArH), 6.50(1H, dd, J¼ 2.4,7.8Hz,
ArH), 6.47 (1H, d, J ¼ 2.4 Hz, ArH), 6.45 (1H, dd, J ¼ 2.4, 7.8 Hz, ArH),
5.57 (1H, bs, OH), 5.27 (1H, t, J ¼ 8.0 Hz, CH), 5.23 (1H, t, J ¼ 8.0 Hz, CH),
5.13 (1H, m, CH), 5.11 (2H, s, CH2), 5.00 (2H, s, CH2), 4.99 (1H, d,
J ¼ 6.8 Hz, CH), 4.27 (1H, dd, J ¼ 5.4,12.2 Hz, CH2), 4.15 (1H, dd, J ¼ 2.4,
12.2 Hz, CH2), 3.82 (1H, ddd, J ¼ 2.4, 5.4, 8.0 Hz, CH), 2.75 (4H, m, CH2),
2.07(3H, s,CH3), 2.043(3H,s, CH3), 2.037(3H, s,CH3), 2.02(3H, s,CH3).
21 (149 mg, 77% from 19) as a white solid. [
a
]
D
19 ꢃ18.5 (c 0.30, CHCl3).
IR (film) nmax 1755, 1610, 1506, 1221, 1041, 737 mꢃ1
.
1H NMR
(100 MHz, CDCl3)
d
7.38 (10H, m, ArH), 6.99 (1H, d, J ¼ 8.3 Hz, ArH),
13C NMR (100 MHz, CDCl3)
d 171.0 (C),170.6 (C),169.73 (C),169.65 (C),
6.86 (1H, d, J ¼ 8.3 Hz, ArH), 6.68 (1H, d, J ¼ 2.4 Hz, ArH), 6.57 (1H, d,
J ¼ 2.4 Hz, ArH), 6.54 (1H, dd, J ¼ 2.4, 8.3 Hz, ArH), 6.50 (1H, dd, J ¼ 2.4,
8.3 Hz, ArH), 5.15 (6H, m, CH and CH2), 5.02 (4H, m, CH), 4.99 (2H, m,
CH), 4.20 (1H, dd, J ¼ 4.7, 12.1 Hz, CH2), 4.16 (1H, dd, J ¼ 4.7, 12.1 Hz,
CH2), 3.50 (1H, dd, J ¼ 7.8, 11.7 Hz, CH2), 3.47 (1H, dd, J ¼ 7.8, 11.7 Hz,
CH2), 2.80 (4H, m, CH2), 2.04 (18H, m, CH3). 13C NMR (100 MHz,
158.9 (C), 157.3 (C),156.8 (C),155.3 (C),137.2 (C), 136.8 (C), 130.7 (CH),
130.6 (CH),129.0 (CH),128.9 (CH),128.5 (CH),128.3 (CH),127.84 (CH),
127.76 (CH), 123.0 (C), 122.8 (C), 109.2 (CH), 106.1 (CH), 105.1 (CH),
101.3 (CH), 99.6 (CH), 73.1 (CH), 72.3 (CH), 71.5 (CH), 70.6 (CH2), 70.5
(CH2), 68.7 (CH), 62.3 (CH2), 31.6 (CH2), 31.2 (CH2), 20.9 (CH3).
ESIHRMS m/z 755.2700 [M ꢃ H]ꢃ (calcd for C42H43O13, 755.2704).